Antigenic polypeptide fragments of a receptor related to the Fab fragment of human immunoglobulin from thymus-derived lymphocytes.

AUTOR(ES)

Marchalonis, J J

RESUMO

Certain thymus-derived lymphocytes of man and other primates express surface components related to the variable region of immunoglobulin heavy chains but lack constant region determinants defining any known immunoglobulin class. To obtain structural information on this molecule that can be used for comparison with known immunoglobulins and other surface molecules, we isolated the T cell-derived molecule by affinity chromatography using an antiserum raised against the monomeric Fab fragment of a human Waldenström macroglobulin and subjected the isolated molecule to either proteolysis using enzymes or cleavage with cyanogen bromide, followed by isolation of polypeptides which bore the Fab- or heavy chain variable region (VH)-related antigenic markers. The intact T cell molecule had an apparent mass of 68,000 daltons and no evidence was found for covalent or noncovalent association with polypeptides resembling light chains in apparent mass. The pattern of fragments obtained by cleavage of the T cell heavy chain suggests that the molecule is comprised of domains of approximate mass 12,000 daltons. Isolation of fragments from the digests that bear Fab-related serological markers shows that the molecule can be degraded into fragments resembling the Fd and VH of standard immunoglobulin heavy chains. A procedure was developed enabling the isolation of milligram quantities of VH-related T cell products. These results support the concept of a sharing of combining site determinants between T cell receptors and immunoglobulin heavy chains and show a general formal similarity between the two classes of molecules, even though they lack shared constant region determinants. The susceptibility of the T cell molecule to be cleaved into discrete antigenic fragments by controlled proteolysis might help to explain the plethora of sizes observed for antigen-specific T cell factors.

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